Scientists at UofL, along with colleagues from Boston University and the University of Massachusetts Lowell, have identified perfluorooctane sulfonate (PFOS) as a potential environmental factor that worsens alcohol-associated liver disease.

PFOS is a man-made chemical belonging to the group known as per- and polyfluoroalkyl substances (PFAS), often referred to as “forever chemicals” because they do not readily break down in the environment or the human body. These substances have been used for decades in products such as non-stick cookware, water-resistant clothing, fast-food packaging, stain-resistant carpets and upholstery, and firefighting foams. Their extensive use has led to widespread contamination in the environment. show that PFAS can be detected in approximately 95% of Americans, sparking increasing concern about their long-term health effects.

At the same time, alcohol consumption remains a significant global health issue. , and its consumption continues to rise globally. In the U.S. alone, excessive alcohol use is responsible for approximately 95,000 deaths annually, making it one of the leading causes of preventable death and a major contributor to liver disease.

“Given the increasing prevalence of alcohol consumption and the widespread presence of PFAS in the environment, many individuals who drink alcohol may be inevitably exposed to these persistent pollutants. This makes it critically important to study how combined exposures to alcohol and environmental chemicals like PFOS might influence liver health,” said Matthew Cave, UofL professor of medicine and publication co-author.

Although it is well known that both alcohol and PFOS cause liver damage individually, little has been understood about their combined effects until now. , indicating that additional factors such as genetics, sex, microbiome and environmental exposures may contribute to individual susceptibility.

“This work helps explain why two people with similar alcohol consumption may experience very different liver outcomes,” said Frederick Ekuban, assistant professor of medicine at UofL and first author of the study. “Environmental exposures like PFOS may be the missing link.”

Using animal models, the researchers simulated real-world exposures to both alcohol and PFOS. The study showed that co-exposure to alcohol and PFOS significantly increased fat accumulation and markers of liver damage, as well as clear signs of disrupted metabolism and activation of genes and pathways predicted to be associated with oxidative stress and cancer development.

In short, the study demonstrates that PFOS exposure can significantly worsen liver damage when combined with alcohol consumption. While this research used high levels of alcohol to understand the underlying mechanisms, the findings reveal important biological pathways that warrant further investigation across different drinking patterns.

The research team also found that PFOS interferes with the liver’s ability to manage fats, disrupts its natural protective and repair systems and activates pathways that promote liver injury.

“While the liver typically has a remarkable capacity to recover from alcohol-induced stress, PFOS appears to push that resilience beyond its limits, resulting in compounded and more severe damage,” said Jennifer Schlezinger professor of environmental health at Boston University and co-author of the publication.

Perhaps most concerning, the team discovered that 60% of all PFOS exposure ended up concentrated in the liver, exactly where alcohol damage occurs.

Ongoing research at UofL is examining how other PFAS compounds may interact with alcohol, whether males and females respond differently to these exposures and what the long-term consequences of combined exposures might be. The team is also exploring whether targeted therapies can be developed to prevent or mitigate this type of liver damage.

Although more studies are needed, people can take practical steps now to limit their exposure to PFAS. These include:

• Choose stainless steel or cast-iron cookware instead of non-stick pans
• Use water filters, especially in areas near industrial zones
• Avoid stain-resistant treatments on furniture and carpets
• Reduce consumption of packaged fast foods and microwave popcorn.
• Select household products with PFAS-free labels

Given that liver disease affects millions of Americans and is becoming more prevalent worldwide, the findings of this research support growing calls for stronger regulation and oversight of persistent chemical contaminants. By better understanding the hidden interactions between environmental toxicants and lifestyle behaviors, scientists and policymakers may be better equipped to prevent and treat liver disease.

 Article by Sarah Jump

University of Louisville environmental medicine researchers are working to better understand how natural, social and personal environments affect health, particularly the cardiovascular system. In recent months, the National Institutes of Health have awarded four grants totaling $11.6 million to researchers affiliated with UofL’s to study factors affecting heart health. Through these projects, they hope to better understand how environmental exposures and tobacco products can affect the cardiovascular system, as well as how remodeling takes place in the heart after a heart attack.

“The unique and synergistic research collaborative we have built at the Envirome Institute already has resulted in new discoveries about the biological and the environmental factors that contribute to heart disease,” said Aruni Bhatnagar, chief of the UofL Division of Environmental Medicine and director of the Envirome Institute. “Our studies funded by these new grants will lead to better understanding of the causes and progression of cardiovascular disease and new ways to protect and improve cardiovascular health.”

The new projects address the cardiovascular effects of newly introduced ingredients in electronic cigarette liquids, exposure to benzene, prenatal and infant exposure to combinations of substances and their impact on sleep in adolescence and the metabolic processes occurring after a heart attack that result in scarring in the heart.

One grant provides $3.3 million to investigate how exposure to benzene affects blood vessels. Sanjay Srivastava, professor of medicine who leads the project, said preliminary research shows that benzene worsens atherosclerosis, an underlying cause of cardiovascular disease and stroke. Atherosclerosis, a buildup of fatty deposits in arteries, reduces blood flow and flexibility of the arteries. Benzene is one of the top 20 pollutants from industrial sources in the United States, primarily from gasoline refineries. Outside industrial locations, exposure is higher near gas stations and from automobile exhaust and cigarette smoke. Benzene is known to cause cancer, but this is the first study to evaluate the effects of the chemical on heart disease, especially at levels typically experienced in the environment.

Cardiac fibrosis is essential for upholding the structure of the heart after heart attack, but also tends to produce excessive scar tissue and stiffening of the heart. Bradford Hill is examining the processes behind stiffening and scarring in the heart following myocardial infarction. A $2.3 million grant is funding the professor of medicine’s work to investigate the metabolic processes underlying this process. Hill hopes the work will lead to a therapy that supports the repair process but also reduces excessive scarring, allowing heart attack patients to fare better down the road.

Clara Sears, assistant professor of environmental medicine, received a $2.1 million grant for a project to discover how exposure to mixtures of common chemicals and pollutants before birth and in infancy affects sleep health in adolescence. Ultimately, she hopes to understand whether exposures to phthalates (common components of plastics), metals and per-/polyfluoroalkyl substances (PFAS – known as “forever chemicals”) may be linked to cardiovascular issues later in life.

The largest of the grants, $3.9 million, will fund research into potential toxicity of new synthetic cooling compounds that are being used in electronic cigarette liquids. Daniel J. Conklin leads the project to learn whether these compounds are harmful to the cardiovascular and pulmonary systems when heated and inhaled. The compounds mimic the cooling effect of menthol, which can be irritating in high doses, but they have not been tested for safety or toxicity as inhaled substances. For this new project, Conklin, a professor of medicine who has studied the cardiovascular effects of e-cigarette and cigarette components for more than two decades, is testing the effects of the new constituents as well as documenting the impact of dual use – smoking conventional cigarettes along with vaping. The Food and Drug Administration’s Center for Tobacco Products will use the results of these studies to determine potential recommendations to regulate the products’ use.

“We are going to address the issue of dual use, where there are both cigarettes and e-cigarettes in use, because this is a very common phenomenon and the signals are coming that it’s actually worse than either one alone,” Conklin said.

“Everyone sleeps and it’s fascinating to me. We know so little about sleep scientifically that it really piqued my interest, and my project is right at the intersection of cardiovascular health and neurodevelopment, so it is kind of the perfect niche for my interest,” said Sears, assistant professor of environmental medicine, a researcher in the University of Louisville’s and a UofL alumna.

Sears is leading a project to discover how exposure to mixtures of common chemicals and pollutants during gestation and infancy affects sleep health in adolescence. Ultimately, she believes the exposures may be linked to cardiovascular issues later in life. Her work is part of research at the Envirome Institute to understand relationships between the environment and human health.

“Sleep is increasingly recognized to be central to cardiovascular health. We know that a variety of lifestyle choices and environmental factors affect sleep, but we know little about the effects of chemical exposure and pollutants,” said Aruni Bhatnagar, professor of medicine and director the Envirome Institute. “Clara’s work could provide new knowledge about factors that affect sleep, particularly in adolescents, so that we can improve their quality of sleep and future cardiovascular health.”

Sears’ team is examining exposure to combinations of phthalates (common components of plastics), metals and per-/polyfluoroalkyl substances (PFAS – known as “forever chemicals”). People are frequently exposed to these toxicants through their diet, as well as use of consumer goods and household products. Sears said they chose to study mixtures rather than individual chemicals because most people in the U.S. are exposed to them in combination.

“We know pregnant women and children are exposed to these chemicals in mixtures and sometimes they can affect similar biological pathways, or they can interact in ways that may magnify an effect on a health outcome,” Sears said. “So, if we study them in isolation, it is hard to get the real-world relevance of how they interact with each other to affect health.”

The work is funded by a five-year, $2.1 million grant from the National Institutes of Health to determine whether there are connections between these early exposures and poor sleep quality and increases in allostatic load in adolescents. Allostatic load is the cumulative burden of “wear and tear” on the body resulting from stressors that eventually can disrupt an individual’s immune, cardiovascular and metabolic functions. A person’s allostatic load can be assessed through biomarkers and other measures such as inflammation and body composition.

Sears is working with experts in pediatric environmental health, sleep and cardiometabolic health to analyze data from two long-term studies that track prenatal and early life exposures and other health information. The Health Outcomes and Measures of the Environment Study and the Maternal-Infant Research on Environmental Chemicals Study have documented exposures and other health measures in more than 550 children from before birth through pre-teen and teen years, along with sleep health in adolescence.

Sears hopes the study will lead to understanding the link between early life environmental factors and cardiovascular health later in life, informing efforts to improve the environment for infants and children so that they can be healthier into adulthood.

“Sleep impacts every aspect of your health and your day-to-day functioning, so if we can find ways to improve sleep it can have huge impacts on health overall.”

See previous sleep research from the Envirome Institute: Reduced sleep linked to environmental factors | UofL News.